Asymmetric aldol additions: Use of titanium tetrachloride and (-)-sparteine for the soft enolization of N-acyl oxazolidinones, oxazolidinethiones, and thiazolidinethiones
Mt. Crimmins et al., Asymmetric aldol additions: Use of titanium tetrachloride and (-)-sparteine for the soft enolization of N-acyl oxazolidinones, oxazolidinethiones, and thiazolidinethiones, J ORG CHEM, 66(3), 2001, pp. 894-902
Asymmetric aldol additions using chlorotitanium enolates of N-acyloxazolidi
none, oxazolidinethione, and thiazolidinethione propionates proceed with hi
gh diastereoselectivity for the Evans or non-Evans syn product depending on
the nature and amount of the base used. With 1 equiv of titanium tetrachlo
ride and 2 equiv of (-)-sparteine as the base or 1 equiv of(-)-sparteine an
d 1 equiv of N-methyl-2-pyrrolidinone, selectivities of 97:3 to >99:1 were
obtained for the Evans syn aldol products using N-propionyl oxazolidinones,
oxazolidinethiones, and thiazolidinethiones. The non-Evans syn aldol adduc
ts are available with the oxazolidinethione and thiazolidinethiones by alte
ring the Lewis acid/amine base ratios. The change in facial selectivity in
the aldol additions is proposed to be a result of switching of mechanistic
pathways between chelated and nonchelated transition states, The auxiliarie
s can be reductively removed or cleaved by nucleophilic acyl substitution.
Iterative aldol sequences with high diastereoselectivity can also be accomp
lished.